Vaccines

16 pages, 2410 KB

Open AccessEditor’s ChoiceArticle

Geographical Patterns of COVID-19 Vaccine Inequality by Race and Ethnicity and Sociodemographic Determinants of Health: Evidence from Louisville, Kentucky

by Seyed M. Karimi, Amir Hossein Hassani, Hamid Zarei, Mana Moghadami, Md Yasin Ali Parh, Shaminul H. Shakib, Venetia Aranha, Mohammad Mansouri, Trey Allen, Yuting Chen, Sirajum Munira Khan, Farzaneh Raoofi, Sepideh Poursafargholi, Taylor Ingram and Angela Graham

Vaccines 2025, 13(12), 1241; https://doi.org/10.3390/vaccines13121241 - 13 Dec 2025

Cited by 2 | Viewed by 1804

Abstract

Background: Infectious diseases accounted for approximately 18.4% of global mortality in 2019. According to the World Health Organization (WHO), vaccines are available for about 30 potentially lethal diseases. Vaccination prevents substantial mortality and hospitalization. However, its ability to improve overall public health depends [...] Read more.

Background: Infectious diseases accounted for approximately 18.4% of global mortality in 2019. According to the World Health Organization (WHO), vaccines are available for about 30 potentially lethal diseases. Vaccination prevents substantial mortality and hospitalization. However, its ability to improve overall public health depends on equitable access across all populations, regardless of race, ethnicity, education, or socioeconomic status. Objectives: This study aims to examine how disparities in social determinants of health (SDOH) affect COVID-19 vaccination uptake across Jefferson County, Kentucky. Using ZIP code–level spatial mapping, this study investigates the intersection of SDOH, racial composition, and geographic characteristics to identify inequities and inform equitable interventions. Methods: Data from the Kentucky Immunization Registry (KYIR) were analyzed to assess two-dose COVID-19 vaccination rates at the ZIP code and regional levels in Jefferson County, Kentucky. Vaccination rates were stratified by race and ethnicity and linked with SDOH, including education, employment, insurance status, and income, obtained from the 2021 American Community Survey. Results: By May 2021, vaccination rates ranged from 25.9% in the West region to 57.0% in the Inner East region; by May 2022, these rates increased to 46.2% and 73.9%, respectively. White residents consistently had the highest two-dose vaccination rates (66.4% by May 2022), while Black and Hispanic residents had lower rates (45.7% and 43.9%, respectively). Vaccination rates were strongly correlated with SDOH, especially educational attainment, average family income, and employment rate, underscoring the role of socioeconomic inequities in vaccination disparities. Conclusions: Geographical and racial disparities emphasize the influence of social and economic inequality on vaccine uptake. Full article

(This article belongs to the Special Issue Vaccines and Vaccinations During and After the Pandemic Period)

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26 pages, 3353 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Polymyxin B as a Novel Vaccine Adjuvant and Its Immunological Comparison with FDA-Approved Adjuvants

by Mahek Gulani, Yash Harsoda, Tanisha Arte, Martin J. D’Souza, Priyal Bagwe, Emmanuel Adediran, Nigel D’Souza and Dedeepya Pasupuleti

Vaccines 2025, 13(12), 1232; https://doi.org/10.3390/vaccines13121232 - 9 Dec 2025

Cited by 2 | Viewed by 1410

Abstract

Background: Adjuvants enhance the immune response to antigens incorporated in vaccine formulations. Given that the majority of infectious agents enter the body through mucosal surfaces, efficacious vaccines must generate protective immunity at these sites, which serve as the first line of defense. There [...] Read more.

Background: Adjuvants enhance the immune response to antigens incorporated in vaccine formulations. Given that the majority of infectious agents enter the body through mucosal surfaces, efficacious vaccines must generate protective immunity at these sites, which serve as the first line of defense. There is a need for mucosal adjuvants; hence, we explored the potential of repurposing existing drugs with established safety profiles in humans. Polymyxins are a class of clinically used antibiotics. They are cationic peptides and mast cell activators, which are a novel class of vaccination adjuvants. The goal was to assess the adjuvant properties of Polymyxin B microparticles in combination with vaccine candidates previously developed in our laboratory, such as microparticulate gonorrhea, influenza, measles, Zika, and canine coronavirus vaccines, and to compare their performance with FDA-licensed adjuvants, such as MF59 and Alum. Methods: Polymyxin microparticles were formulated using a double emulsion method, and the toxicity profile and autophagosome generation of Polymyxin B microparticles were assessed. The immunogenic potential of Polymyxin B in these vaccines was studied using multiple parameters such as nitric oxide release using Griess assay and immune profiling using flow cytometry for markers such as MHC I, MHC II, CD40, and CD80. Results: Polymyxin B microparticles were found to be non-cytotoxic to dendritic cells up to 500 μg/mL. Polymyxin B promoted autophagosome formation and nitric oxide release, and showed the upregulation of MHC I, MHC II, CD80, and CD40 pathways. Conclusions: The adjuvant activity of Polymyxin B across various vaccine platforms is significantly comparable to FDA-approved adjuvants, which is a critical requirement for generating T cell responses such as helper T cell and cytotoxic CD8+ T cell responses. Full article

(This article belongs to the Special Issue Bioengineering in Vaccine Design and Delivery)

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23 pages, 1448 KB

Open AccessEditor’s ChoiceReview

Engineering Anti-Tumor Immunity: An Immunological Framework for mRNA Cancer Vaccines

by Olivia Roy and Karen S. Anderson

Vaccines 2025, 13(12), 1222; https://doi.org/10.3390/vaccines13121222 - 3 Dec 2025

Cited by 2 | Viewed by 3202

Abstract

The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer [...] Read more.

The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer vaccine development. Achieving durable clinical benefit requires more than antigen expression. Effective vaccines need precise epitope selection, optimized delivery systems, and rigorous immune monitoring. The field is shifting from merely inducing immune responses to focusing more on the biochemistry and molecular design principles that combine magnitude, polyfunctionality, and longevity to overcome tumor-induced immune suppression. We examine an integrated immunological framework for mRNA cancer vaccine development, examining how rational molecular engineering of vaccine components, from nucleoside modifications and codon optimization to untranslated regions and linker sequences, shapes immunogenicity and therapeutic efficacy. Future directions will depend on balancing combinatorial strategies combining vaccination with immune checkpoint inhibitors and adoptive cell therapies. Full article

(This article belongs to the Special Issue Vaccines Targeting the Tumor Microenvironment: Challenges and Future Prospects)

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15 pages, 779 KB

Open AccessEditor’s ChoiceArticle

Assessing COVID-19 Infection and Severe Disease Risk in Cancer Patients and Survivors: The Role of Vaccination Status, Circulating Variants, and Comorbidities—A Population-Based Study in Northern Italy

by Massimo Vicentini, Pamela Mancuso, Francesco Venturelli, Sergio Mezzadri, Eufemia Bisaccia, Alessandro Zerbini, Lucia Mangone, Paolo Giorgi Rossi and on behalf of the Reggio Emilia COVID-19 Working Group

Vaccines 2025, 13(12), 1223; https://doi.org/10.3390/vaccines13121223 - 3 Dec 2025

Viewed by 4061

Abstract

Background: Cancer patients are particularly vulnerable to severe outcomes from COVID-19 due to immune suppression, treatment effects, and comorbidities. This population-based study aimed to assess how vaccination, circulating variants, and comorbidities influenced infections and severe disease risks in cancer patients compared with [...] Read more.

Background: Cancer patients are particularly vulnerable to severe outcomes from COVID-19 due to immune suppression, treatment effects, and comorbidities. This population-based study aimed to assess how vaccination, circulating variants, and comorbidities influenced infections and severe disease risks in cancer patients compared with the general population. Methods: The study included 538,516 residents of Reggio Emilia Province, Italy, alive on 20 February 2020, followed until 30 September 2022. Cancer diagnoses (1996–2021) were obtained from the Reggio Emilia Cancer Registry and linked with COVID-19 surveillance, vaccination, hospitalization, and mortality data. Vaccination and prior infection were modelled as time-dependent variables. Hazard ratios for infection (HRs) and odds ratios for severe disease in those infected (ORs) were estimated using Cox and logistic regression models adjusting for sex, age, and comorbidities. Results: Among the 33,307 residents who had cancer, 9135 SARS-CoV-2 infections were recorded. Infection risk was similar to the general population before Omicron (HR 1.00; 95%CI 0.96–1.05) and slightly higher during Omicron (HR 1.08; 95%CI 1.05–1.11). Cancer patients showed higher probability of severe disease once infected (OR 1.33 pre-Omicron; 1.67 Omicron), with the greatest excess in recent diagnoses. Vaccination substantially reduced infections and severe outcomes in both groups in the pre-Omicron period; while only hybrid immunity reached high protection from Omicron infection. Conclusions: Vaccinations were effective in the populations with and without cancer; hybrid immunity conferred the strongest protection. However, because cancer patients, especially those recently diagnosed, retain a higher baseline risk of severe disease, vaccination yields even greater individual and public health benefits. Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

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14 pages, 2118 KB

Open AccessEditor’s ChoiceArticle

Impact of a Universal Nirsevimab Prevention Program Against Respiratory Syncytial Virus Bronchiolitis in Infants in Sicily (Italy) During the 2024–2025 Epidemic Season: A Retrospective Cohort Study

by Claudio Costantino, Emanuele Amodio, Rosario Asciutto, Costanza Affranchi, Franco Belbruno, Nicole Bonaccorso, Sonia Cilia, Fabio Massimo Contarino, Vincenzo Di Gaetano, Francesco Di Gregorio, Angelo Foresta, Roberto Furnari, Flavio Genna, Dario Genovese, Gabriele Giorgianni, Carmelo Massimo Maida, Sara Palmeri, Giovanna Parrino, Alessandra Piazza, Sebastiano Pollina Addario, Giovanni Tinervia, Fabio Tramuto and Francesco Vitale Show full author list Hide full author list

Vaccines 2025, 13(12), 1219; https://doi.org/10.3390/vaccines13121219 - 2 Dec 2025

Cited by 6 | Viewed by 1949

Abstract

Objectives: The introduction of universal prophylaxis with Nirsevimab represents a major innovation in preventing respiratory syncytial virus (RSV) infections in newborns. In Sicily, Nirsevimab administration began on 1 November 2024, for all newborns under one year and at-risk infants during the 2024–2025 [...] Read more.

Objectives: The introduction of universal prophylaxis with Nirsevimab represents a major innovation in preventing respiratory syncytial virus (RSV) infections in newborns. In Sicily, Nirsevimab administration began on 1 November 2024, for all newborns under one year and at-risk infants during the 2024–2025 season. This study assessed the real-world impact of this strategy in reducing RSV-related hospitalizations. Methods: This retrospective cohort study examined newborns residing in Sicily from 2015 to May 2025, evaluating hospitalization incidence rates attributable to RSV during the first year of life. RSV hospitalizations were identified using ICD-9 codes (079.6, 466.11, 480.1) in any diagnostic position. Incidence rates in the 2024–2025 season (intervention period) were compared with preceding seasons. Results: During the study period, 4431 RSV hospitalization cases occurred (19.84 cases per 1000 person-years), peaking in 2023–2024 (53.47 cases per 1000 person-years). A statistically significant 40% reduction in RSV hospitalizations was observed during the 2024–2025 season (October–April) compared with the preceding season, with a relative reduction ranging between 33.4% and 54.8% across sensitivity models. Conclusions: These results confirm the significant impact of the universal prophylaxis program in real-world practice, consistent with other European programs. These findings support universal RSV prevention strategies and provide insights for optimizing regional and national health policies. Full article

(This article belongs to the Section Vaccines and Public Health)

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17 pages, 3216 KB

Open AccessEditor’s ChoiceArticle

The DNA Vaccines for the Gn and Gc Heterologous Polymer of Severe Fever with Thrombocytopenia Syndrome Virus Induce Potent Immunogenicity in Mice

by Qiuju He, Xiaojuan Liu, Jincheng Tong, Huan Li, Heng Zhang, Jiamin Chen, Mengyi Zhang, Zhihua Li and Qianqian Li

Vaccines 2025, 13(12), 1186; https://doi.org/10.3390/vaccines13121186 - 24 Nov 2025

Cited by 2 | Viewed by 1205

Abstract

Introduction/Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a threat to global public health with a mortality rate of up to 30%. However, there is currently no commercialized SFTSV vaccine. This study focused on the construction of DNA vaccines with different structures [...] Read more.

Introduction/Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a threat to global public health with a mortality rate of up to 30%. However, there is currently no commercialized SFTSV vaccine. This study focused on the construction of DNA vaccines with different structures based on the surface glycoproteins Gn and Gc to identify the immunodominant conformations. Methods: The DNA vaccines encoding secretory proteins including Gn or Gc monomer, heterodimer of Gn and Gc (dimer), two forms of hexamer composed of the Gn and Gc heterodimer (hexamer-1 and hexamer-2) or ferritin nanoparticles of Gn, and non-secretory proteins including Gn (Gn-TM) and Gc (Gc-TM) were constructed. Western blot confirmed the expression level and the specificity of those DNA vaccines. After vaccinating mice with those DNA vaccines, its induced humoral and cellular immunity were comprehensively evaluated. Results: The DNA vaccines were constructed successfully. The DNA vaccines of Gn and polymers including dimer, hexamer-2, and ferritin nanoparticles inducing stronger binding antibody, neutralizing antibody, and antibody-dependent cellular cytotoxicity (ADCC) activity. The neutralizing antibody induced by these constructs was also cross-recognized by other five SFTSV pseudovirus strains. However, the T cell response induced by Gc, dimer or hexamer-2 DNA vaccines were significantly higher than those in most other groups, including Gn. Conclusion: The DNA vaccines encoding dimer or hexamer-2 demonstrated superior immunogenicity over other conformations, after taking the results of humoral and cellular responses into account. This study revealed the advantages of using polymer conformations in SFTSV vaccine design and provided new targets in SFTSV vaccine development. Full article

(This article belongs to the Special Issue The Development of Recombinant and Subunit Vaccines Against Infectious Diseases)

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22 pages, 1635 KB

Open AccessEditor’s ChoiceReview

Self-Assembled Peptides: A New Generation of Vaccine Adjuvant Platform

by Miao-Miao Zhang, Ji Zhu, Zhao-Yi Wang, Yu-Lun Bai, Hai-Bo Li, Buhe Nashun and Yue Jiang

Vaccines 2025, 13(12), 1183; https://doi.org/10.3390/vaccines13121183 - 21 Nov 2025

Cited by 3 | Viewed by 2619

Abstract

The advent of precision medicine has spotlighted subunit and peptide-based vaccines, which offer high safety but often require potent adjuvants to enhance immunogenicity. Self-assembled peptides have emerged as a promising adjuvant platform due to their ease of synthesis, excellent biocompatibility, and tunable structural [...] Read more.

The advent of precision medicine has spotlighted subunit and peptide-based vaccines, which offer high safety but often require potent adjuvants to enhance immunogenicity. Self-assembled peptides have emerged as a promising adjuvant platform due to their ease of synthesis, excellent biocompatibility, and tunable structural properties. Recent advances highlight their potential in boosting vaccine efficacy, with self-assembled peptides forming highly ordered architectures that are conducive to immune system activation. This review discusses the key factors driving peptide self-assembly and explores their evolving role as innovative vaccine adjuvants, alongside challenges and future development directions. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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14 pages, 1397 KB

Open AccessEditor’s ChoiceArticle

Influenza Vaccination in the Elderly in Three Cities in China: Current Status and Influencing Factors Under Different Funding Policies

by Rina Su, Hongting Zhao, Xiaokun Yang, Ying Qin, Jiandong Zheng, Xinyi Liu, Xinwei Du and Zhibin Peng

Vaccines 2025, 13(11), 1158; https://doi.org/10.3390/vaccines13111158 - 12 Nov 2025

Cited by 2 | Viewed by 1631

Abstract

Background: Influenza is a major health threat to the elderly in China. Despite this, influenza vaccination rates still remain low and vary across regions that have different funding policies. In this study, we compare the vaccination status and influencing factors among older [...] Read more.

Background: Influenza is a major health threat to the elderly in China. Despite this, influenza vaccination rates still remain low and vary across regions that have different funding policies. In this study, we compare the vaccination status and influencing factors among older adults under the free, partial reimbursement, and self-paid vaccination strategies. Methods: Three cities with free, partial reimbursement, and self-paid influenza vaccination policies were selected. A cross-sectional, anonymous survey was then conducted. A total of 2265 elderly individuals aged 60 years and above were recruited using probability proportionate to size sampling. A standardized questionnaire was used during face-to-face interviews to collect data regarding the influenza vaccination status and influencing factors. The statistical analyses included chi-square tests, a multivariate logistic regression, and random forest models. Results: Among the 2265 participants (free policy region: n = 426; partial reimbursement region: n = 633; self-paid region: n = 1206), vaccination rates during the 2023–2024 season were significantly higher in the free policy region (53.29%) than in the partial reimbursement (20.85%) and self-paid (13.60%) regions (p < 0.001). The intention to vaccinate for the 2024–2025 season was also highest in the free policy region (68.78%), followed by partial reimbursement (47.71%) and self-paid (37.15%) regions (p < 0.001). This result demonstrated the same trend as the vaccination behavior. Cues to action (e.g., healthcare worker or family member recommendations) positively influenced vaccinations across all of the regions. In the self-paid region, perceived barriers, such as vaccine cost and side effect concerns, significantly reduced both behaviors and the next-season intention to vaccinate. Healthcare worker recommendations were key positive factors, while misconceptions and costs were major barriers to vaccination. Conclusions: Vaccination rates varied significantly across regions with different influenza vaccine subsidy policies. The free policy region demonstrated the highest coverage rate, while the self-paid region exhibited the lowest, suggesting that financial policies are a key determinant of vaccination uptake. Furthermore, free vaccination policies were associated with improved influenza vaccine knowledge among the elderly. Analysis of other influencing factors revealed that healthcare workers’ recommendations played a crucial role across all policy regions, though their impact on current-season vaccination behavior and next-season vaccination intention differed by subsidy context. Further studies are needed to explore the best approaches for optimizing region-specific subsidy strategies for promoting influenza vaccination among the elderly in China. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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18 pages, 1162 KB

Open AccessEditor’s ChoiceReview

Shaping Antitumor Immunity with Peptide Vaccines: Implications of Immune Modulation at the Vaccine Site

by Amrita Sarkar, Emily Pauline Rabinovich and Craig Lee Slingluff, Jr.

Vaccines 2025, 13(11), 1150; https://doi.org/10.3390/vaccines13111150 - 11 Nov 2025

Cited by 2 | Viewed by 1746

Abstract

Cancer vaccines have emerged as a class of therapeutics designed to harness the immune system to stimulate durable anti-tumor responses with lower systemic toxicity than conventional therapies. Many platforms have been explored, including protein, peptide, DNA, RNA, and cell-based vaccines. Within this landscape, [...] Read more.

Cancer vaccines have emerged as a class of therapeutics designed to harness the immune system to stimulate durable anti-tumor responses with lower systemic toxicity than conventional therapies. Many platforms have been explored, including protein, peptide, DNA, RNA, and cell-based vaccines. Within this landscape, peptide vaccines remain a promising approach. Most clinical trials have examined peripheral immune responses and clinical outcomes, but there is growing interest in the vaccine site microenvironment (VSME) as a window to understand local immune activation and its implications for systemic immunity and tumor control. Studies of the VSME have investigated the effects of adjuvants, local immune cell dynamics, and their correlation with systemic responses and outcomes. Local adjuvants typically enhance immune cell infiltration, though there are concerns regarding VSME sequestration or dysfunction of immune cells, which could impact systemic efficacy. Repeated vaccination at a single site may improve antigen presentation and immune responses, but factors such as injection site location may be linked to variability in clinical outcomes. Current studies are limited by substantial variability in sampling, timing, and analyses used in VSME assessment. This limits the comparability of findings and broader inferences regarding the influence of vaccine site dynamics on therapeutic efficacy. Standardized VSME assessment as part of future vaccine trials may improve evaluation of immune responses and provide a more consistent surrogate for vaccine effectiveness. This refinement may inform optimal vaccine strategies and further support the development of next-generation cancer immunotherapies. Full article

(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)

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12 pages, 526 KB

Open AccessEditor’s ChoiceArticle

HPV Vaccination and CIN3+ Among Women Aged 25–29 Years in Northern Norway, 2010–2024: A Population-Based Time-Series Analysis

by Sveinung Wergeland Sørbye, Mona Antonsen and Elin Synnøve Mortensen

Vaccines 2025, 13(11), 1147; https://doi.org/10.3390/vaccines13111147 - 9 Nov 2025

Cited by 1 | Viewed by 2154

Abstract

Background/Objectives: Cervical intraepithelial neoplasia grade 3 and worse (CIN3+) is a robust surrogate for cervical cancer risk. In Norway, organized cervical screening starts at 25 years of age (25–69 years). Norway introduced school-based HPV vaccination with the quadrivalent vaccine for 12-year-old girls in [...] Read more.

Background/Objectives: Cervical intraepithelial neoplasia grade 3 and worse (CIN3+) is a robust surrogate for cervical cancer risk. In Norway, organized cervical screening starts at 25 years of age (25–69 years). Norway introduced school-based HPV vaccination with the quadrivalent vaccine for 12-year-old girls in 2009 (birth cohorts ≥ 1997) with high 3-dose completion, and a catch-up program with the bivalent vaccine for women born 1991–1996 in 2016–2019 with lower uptake. We assessed whether increasing birth-cohort vaccination coverage (defined as ≥1 dose) was followed by reductions in CIN3+ at the age of entry to organized screening (25–29 years). Methods: We conducted a retrospective, population-based time-series of women aged 25–29 years in Troms and Finnmark screened in 2010–2024. CIN3+ was counted per unique woman and expressed per 1000 screened women per year. Cohort-level vaccination exposure was proxied by birth-year eligibility and national coverage (≥1 dose) by calendar year. Temporal trends were assessed using segmented linear regression (2010–2017; 2017–2024). Results: Among 42,253 screening tests, 865 women had CIN3+. CIN3+ rates were stable in 2010–2016 (≈15–24 per 1000), peaked in 2017–2018 (≈26–28 per 1000), and declined to 6.6 per 1000 in 2024 (~75% reduction from the peak). The 2010–2017 trend was not significant (p = 0.244), whereas 2017–2024 showed a significant annual decline (slope −3.04 per 1000 per year; p = 7.4 × 10⁻⁵). The decline coincided with an increase in the vaccinated share of the age group from an estimated 12% in 2017 to 78% in 2024. Cervical cancer was rare throughout and absent in 2024, and the 2023 transition to primary HPV testing did not interrupt the downward trend. Conclusions: As vaccinated birth cohorts—especially those vaccinated before sexual debut—entered organized screening at age 25, CIN3+ in women aged 25–29 years fell markedly. Estimates are based on coverage defined as ≥1 dose; future linkage to individual dose data and HPV type–specific CIN3+ is warranted. Full article

(This article belongs to the Special Issue HPV Vaccination and Primary HPV Screening)

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28 pages, 671 KB

Open AccessEditor’s ChoiceReview

In Situ Vaccination by Tumor Ablation: Principles and Prospects for Systemic Antitumor Immunity

by Tinatin Chikovani and Eli Magen

Vaccines 2025, 13(11), 1114; https://doi.org/10.3390/vaccines13111114 - 30 Oct 2025

Cited by 8 | Viewed by 3020

Abstract

Cancer immunotherapy has redefined oncology’s goals, aiming for durable systemic immunity rather than mere cytoreduction. However, many solid tumors remain refractory due to immunosuppressive microenvironments and antigenic heterogeneity. Local tumor ablation techniques—including radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, irreversible electroporation (IRE), and [...] Read more.

Cancer immunotherapy has redefined oncology’s goals, aiming for durable systemic immunity rather than mere cytoreduction. However, many solid tumors remain refractory due to immunosuppressive microenvironments and antigenic heterogeneity. Local tumor ablation techniques—including radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, irreversible electroporation (IRE), and high-intensity focused ultrasound (HIFU)—are being re-evaluated beyond their historic cytoreductive role. This comprehensive review synthesizes the paradigm of tumor ablation as an in situ vaccination strategy, a concept that leverages the tumor itself as a source of antigens and the ablation process to generate endogenous adjuvants. We detail the mechanistic underpinnings, highlighting how ablation induces immunogenic cell death (ICD), releasing damage-associated molecular patterns (DAMPs) such as calreticulin, ATP, HMGB1, and cytosolic DNA. These signals activate innate immunity via pathways like cGAS-STING, promote dendritic cell maturation, and facilitate epitope spreading. We critically examine the determinants of efficacy, including the critical impact of ablation modality on the “DAMP signature,” the necessity of complete ablation, and the pivotal role of the host’s immune contexture. Furthermore, we explore the induction of tertiary lymphoid structures (TLS) as a key anatomical site for sustained immune priming. Translational strategies are extensively discussed, focusing on optimizing procedural techniques, rationally combining ablation with immune checkpoint inhibitors (ICIs) and innate immune agonists, and developing a robust biomarker framework. By adopting the core principles of vaccinology—meticulous attention to antigen, adjuvant, route, and schedule—ablation can be engineered into a reproducible platform for systemic immunotherapy. This review concludes by addressing current limitations and outlining a roadmap for clinical translation, positioning interventional oncology as a central discipline in the future of immuno-oncology. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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13 pages, 732 KB

Open AccessEditor’s ChoiceReview

Vaccination Against Herpes Zoster in Adults: Current Strategies in European Union Countries

by Manuela Chiavarini, Angela Bechini, Sara Boccalini, Alisa Barash, Enrica Castellana, Alessandro Senape and Paolo Bonanni

Vaccines 2025, 13(10), 1073; https://doi.org/10.3390/vaccines13101073 - 20 Oct 2025

Cited by 4 | Viewed by 5369

Abstract

Background/Objectives: Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation, significantly affects the functional status and quality of life of older adults and immunocompromised individuals. Vaccination represents an effective strategy to reduce the incidence of HZ. Methods: This review offers a cross-sectional [...] Read more.

Background/Objectives: Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation, significantly affects the functional status and quality of life of older adults and immunocompromised individuals. Vaccination represents an effective strategy to reduce the incidence of HZ. Methods: This review offers a cross-sectional assessment of the current landscape of adult herpes zoster vaccination strategies across the 27 EU member states, drawing on data available up to July 2025 from official sources such as the ECDC, the WHO, and national health authorities. Results: HZ vaccination is recommended in 17 EU countries (63%) according to the National Immunization Programs (NIPs) or by other institutional national health documents; in only 7 countries, vaccination is fully covered by the national healthcare system. HZ vaccination is recommended for healthy adults aged ≥50 years in 23.5% of countries (4/17), ≥60 years in 29.4% (5/17), and ≥65 years in 41.2% (7/17). At-risk groups are targeted in 94.1% of countries (16/17), predominantly from age 18 years (14 countries). Conclusions: An overall tendency toward broader HZ vaccination strategies, targeting both older adults and risk groups, is emerging. However, differences among national policies, together with the European Commission’s withdrawal of the live-attenuated Zostavax vaccine effective 1 June 2025, highlight the urgent need for comprehensive, harmonized immunization strategies to ensure adequate coverage of adult HZ vaccination across Europe. Full article

(This article belongs to the Special Issue From Knowledge to Action: Advances in Herpes Zoster Vaccine and Vaccination)

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15 pages, 2603 KB

Open AccessEditor’s ChoiceReview

Global Transmission, Prevention, Control, and Treatment of Mpox Virus in 2025: A Comprehensive Review from Infection Mechanisms to Vaccine Development

by Quan Quan, Nan Wu, Ying-Hua Luo, Yan-Jun Tang, Yan-Zhi Liu, Xi-Chun Huang, Jun-Hao Li, Wan-Xia Ren and Cheng-Hao Jin

Vaccines 2025, 13(10), 1071; https://doi.org/10.3390/vaccines13101071 - 20 Oct 2025

Cited by 5 | Viewed by 2694

Abstract

The World Health Organization (WHO) declared the mpox (MPX) outbreak a public health emergency of international concern (PHEIC) on 23 July 2022, and 14 August 2024, respectively, underscoring the confirmed and concerning global spread of the disease. A gap exists in our fundamental [...] Read more.

The World Health Organization (WHO) declared the mpox (MPX) outbreak a public health emergency of international concern (PHEIC) on 23 July 2022, and 14 August 2024, respectively, underscoring the confirmed and concerning global spread of the disease. A gap exists in our fundamental understanding of the mpox virus (MPXV), despite its genetic relatedness to the variola virus (VARV). This knowledge deficit is evident in the performance of current medical countermeasures; vaccines and antiviral therapies adapted from smallpox programs demonstrate only partial efficacy and are constrained by issues of safety and suboptimal effectiveness against MPXV. In this context, the development of MPX-specific vaccines and antiviral drugs has become a critical priority in the global effort to combat MPX. However, MPXV employs multiple strategies to evade host immune responses, such as producing specific and poxvirus homologous proteins that suppress both innate immunity (including the six principal innate immune signaling pathways and antiviral strategies, notably the interferon [IFN] pathway) and adaptive immunity, thereby complicating vaccine and drug development. Insights from research on vaccinia virus (VACV) and VARV may inform the investigation of MPXV pathogenesis and immune evasion mechanisms. Drawing on relevant scientific literature, this review systematically examines key aspects of MPX infection, pathogenicity, and immune evasion, as well as the coordination between innate and adaptive immune responses. Furthermore, this review elucidates the current application and deployment landscape of the three principal therapeutics and three major vaccines for MPX, aiming to provide a theoretical foundation for future research and development of vaccines and targeted antiviral agents. Full article

(This article belongs to the Section Vaccines and Public Health)

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18 pages, 319 KB

Open AccessEditor’s ChoiceReview

Health Technology Assessment of mRNA Vaccines: Clinical, Economic, and Public Health Implications

by Giovanni Genovese, Caterina Elisabetta Rizzo and Cristina Genovese

Vaccines 2025, 13(10), 1045; https://doi.org/10.3390/vaccines13101045 - 10 Oct 2025

Cited by 2 | Viewed by 5886

Abstract

Health Technology Assessment (HTA) is a multidimensional and multidisciplinary approach for analyzing the medical–clinical, social, organizational, economic, ethical, and legal implications of a technology, through the evaluation of multiple dimensions such as efficacy, safety, costs, and social–organizational impact. In the healthcare context, “technology” [...] Read more.

Health Technology Assessment (HTA) is a multidimensional and multidisciplinary approach for analyzing the medical–clinical, social, organizational, economic, ethical, and legal implications of a technology, through the evaluation of multiple dimensions such as efficacy, safety, costs, and social–organizational impact. In the healthcare context, “technology” refers to any tool—including pharmaceuticals (or, in this case, vaccines)—that is applied to healthcare practice. HTA focuses on assessing both the real and potential effects of a given technology, either prospectively or throughout its life cycle, as well as the consequences that the introduction or exclusion of an intervention may have on the healthcare system, the economy, and society at large. Full article

(This article belongs to the Special Issue Communicable Diseases: New and Old Therapies and Preventive Strategies, 2nd Edition)

28 pages, 1351 KB

Open AccessEditor’s ChoiceArticle

Strengthening Primary Health Care Through Implementation Research: Strategies for Reaching Zero-Dose Children in Low- and Middle-Income Countries’ Immunization Programs

by Boniface Oyugi, Karin Kallander and A. S. M. Shahabuddin

Vaccines 2025, 13(10), 1040; https://doi.org/10.3390/vaccines13101040 - 9 Oct 2025

Cited by 4 | Viewed by 4139

Abstract

Introduction: Despite global improvements in immunization, major gaps persist. By 2024, an estimated 14.3 million infants, predominantly in low- and middle-income countries (LMICs), remained zero-dose (ZD), never having received even the first DTP vaccine. In 2022, 33 million children missed their measles vaccination [...] Read more.

Introduction: Despite global improvements in immunization, major gaps persist. By 2024, an estimated 14.3 million infants, predominantly in low- and middle-income countries (LMICs), remained zero-dose (ZD), never having received even the first DTP vaccine. In 2022, 33 million children missed their measles vaccination (22 million missed the first dose, 11 million missed the second dose), highlighting entrenched structural, behavioral, and systemic barriers that continue to exclude marginalized populations. Addressing these inequities requires innovative, context-adapted approaches that strengthen primary health care (PHC) and extend services to the hardest-to-reach populations. Objectives: This study aims to document and synthesize implementation research (IR) projects on immunization programs in LMICs, identifying key enablers and effective strategies that reduce inequities, improve outcomes, and support efforts to reach ZD children. Methods: We conducted a retrospective multiple-case study of 36 IR projects across 13 LMICs, embedded within an evidence review framework and complemented by policy analysis. Data were drawn from systematic document reviews and validation discussions with project leads. A total of 326 strategies were extracted, coded using a structured codebook, and mapped to the WHO–UNICEF PHC Levers for Action. Descriptive analysis synthesized patterns across service delivery and policy outcomes, including coverage gains, improved microplanning, community engagement, and system integration. Results: Of the 326 immunization strategies identified, most (76.1%) aligned with operational PHC levers, particularly monitoring and evaluation (19.3%), workforce development (18.7%), and models of care (12%). Digital technologies (11.7%) were increasingly deployed for real-time tracking and oversight. Core strategic levers comprised 23.9% of strategies, with community engagement (8.9%) and governance frameworks (7.7%) emerging as critical enablers, though sustainable financing (4%) and private-sector engagement (0.9%) were rarely addressed. While the majority of projects focused on routine immunization (n = 32), only a few directly targeted ZD children (n = 3). Interventions yielded improvements in both service delivery and policy outcomes. Improvements in microplanning and data systems (23.5%) reflected the increased uptake of digital dashboards, GIS-enabled tools, and electronic registries. Community engagement (16.2%) emphasized the influence of local leaders and volunteers in building trust, while health system strengthening (15.7%) invested in cold chain, supervision, and workforce capacity. Coverage gains (10.6%) were achieved through delivery innovations, though sustainable financing remained a critical problem (3.4%). Conclusions: Reaching ZD children requires equity-driven strategies that combine digital innovations, community engagement, and resilient system planning. Sustained progress depends on strengthening governance, financing, and research. Embedding IR in immunization programs generates actionable evidence, supports context-specific strategies, and reduces equity gaps, offering practical insights that complement health system research and advance the Immunization Agenda 2030. Full article

(This article belongs to the Special Issue Inequality in Immunization 2025)

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18 pages, 1585 KB

Open AccessEditor’s ChoiceReview

Understanding Vaccine Hesitancy: Insights and Improvement Strategies Drawn from a Multi-Study Review

by Kaitlin (Quirk) Brumbaugh, Frances Gellert and Ali H. Mokdad

Vaccines 2025, 13(10), 1003; https://doi.org/10.3390/vaccines13101003 - 25 Sep 2025

Cited by 19 | Viewed by 9442

Abstract

Vaccines are among the most effective public health interventions, significantly reducing morbidity and mortality from infectious diseases. Despite their proven efficacy, vaccine hesitancy has emerged as a pressing global challenge. This review examines the drivers, barriers, and interventions associated with vaccine hesitancy and [...] Read more.

Vaccines are among the most effective public health interventions, significantly reducing morbidity and mortality from infectious diseases. Despite their proven efficacy, vaccine hesitancy has emerged as a pressing global challenge. This review examines the drivers, barriers, and interventions associated with vaccine hesitancy and uptake, focusing on childhood vaccinations and the role of parents as primary decision-makers. Misinformation, safety concerns, and political decisions have contributed to declining vaccination rates, posing threats to public health. The article proposes targeted programs and policies to rebuild vaccine confidence, emphasizing the role of trusted messengers, health literacy, and structural reforms to reduce barriers. Recommendations highlight the importance of accurate information, open communication, and advocacy for school vaccine mandates. The conclusion stresses the urgent need to implement robust policies and community-based initiatives to ensure widespread immunization and safeguard population health. Full article

(This article belongs to the Special Issue Impact of Immunization Safety Monitoring on Vaccine Coverage)

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18 pages, 523 KB

Open AccessEditor’s ChoiceSystematic Review

Strategies to Increase Vaccinations in Adult Cancer Patients: A Systematic Review

by Giuseppina Lo Moro, Federica Golzio, Sara Claudia Calabrese, Giacomo Scaioli, Alessandro Basile, Roberta Siliquini and Fabrizio Bert

Vaccines 2025, 13(9), 964; https://doi.org/10.3390/vaccines13090964 - 11 Sep 2025

Cited by 4 | Viewed by 2412

Abstract

Background/Objectives: Although vaccinations are a priority for patients with cancer, achieving high coverage remains challenging. Evidence on effective strategies in oncology settings is still limited. This systematic review aimed to identify interventions to improve vaccination uptake or reduce hesitancy among cancer patients. Methods: [...] Read more.

Background/Objectives: Although vaccinations are a priority for patients with cancer, achieving high coverage remains challenging. Evidence on effective strategies in oncology settings is still limited. This systematic review aimed to identify interventions to improve vaccination uptake or reduce hesitancy among cancer patients. Methods: A systematic search was conducted in PubMed, Embase, and Scopus, including studies published up to the end of 2023. The protocol was registered in PROSPERO (CRD42024511008). Results: Out of 10,927 non-duplicate records, 15 studies describing unique interventions were included. All studies were published between 2011 and 2022, primarily conducted in Europe/UK (40%) and in North America (40%). The most common study design was pre-post (60%), and 33.3% included a control group. Most interventions were multi-component (60%) and were classified into three main categories: educational materials/campaigns (46.7%), reminders (40%), and patient counselling (33.3%). Additional components included guideline development in two studies. Some studies also highlighted the importance of specific key figures, such as dedicated professionals, general practitioners, and pharmacists. Interventions mainly targeted patients (40%), with 33.3% addressing both healthcare professionals and patients and 26.7% professionals only. They most frequently concerned vaccinations against influenza and pneumococcal disease (26.7%), pneumococcal disease alone (26.7%), or Coronavirus Disease 2019 (COVID-19) (26.7%). Vaccination uptake was the primary outcome in 86.7% of studies, with 66.7% reporting significant improvements. Conclusions: This review identified a variety of strategies, with education, reminders, and counselling as key components. Multicomponent interventions and those involving both patients and providers were most promising. However, methodological limitations and limited generalizability highlighted the need for more rigorous research. Full article

(This article belongs to the Special Issue Virus Pandemics and Vaccinations)

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39 pages, 526 KB

Open AccessEditor’s ChoiceReview

Influenza Vaccines: Current Status, Adjuvant Strategies, and Efficacy

by Vijay Reddy Mokalla, Shirisha Gundarapu, Radhey S. Kaushik, Mrigendra Rajput and Hemachand Tummala

Vaccines 2025, 13(9), 962; https://doi.org/10.3390/vaccines13090962 - 11 Sep 2025

Cited by 18 | Viewed by 13578

Abstract

The influenza virus is one of the major global health concerns, causing significant morbidity and mortality in both humans and animals, with substantial impacts on public health. Vaccination remains the primary strategy for managing influenza virus infections; however, the virus undergoes frequent genetic [...] Read more.

The influenza virus is one of the major global health concerns, causing significant morbidity and mortality in both humans and animals, with substantial impacts on public health. Vaccination remains the primary strategy for managing influenza virus infections; however, the virus undergoes frequent genetic changes through antigenic drift and shift. These mutations lead to new seasonal strains that evade pre-existing immunity. These mutations can potentially result in virulent strains that could trigger future pandemics. Therefore, developing a vaccine capable of providing robust protection despite these genetic changes is essential. Vaccine adjuvants are essential for boosting and directing the immune system’s response, broadening the spectrum of protection, and reducing the amount of antigen required to achieve protection, which is particularly valuable in the face of rapidly evolving strains and during pandemics. Recent advances in adjuvant design and formulation strategies have demonstrated promising improvements in both the overall potency and durability of influenza vaccines, importantly, significant reductions in losses due to influenza infection. This review highlights the current status of different types of influenza virus vaccines, their benefits, and challenges. Further, the review focuses on the role of adjuvants, discussing their advantages, limitations, and methodological approaches, while also considering their potential contribution in developing a universal flu vaccine intended to provide extensive and lasting protection. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

21 pages, 2497 KB

Open AccessEditor’s ChoiceReview

Emerging Therapeutic Strategies for Lung Cancer: The Role of Immunotherapy and HPV-Targeted Cancer Vaccines

by Krupa Bhaliya, Muneera Anwer and Ming Q. Wei

Vaccines 2025, 13(9), 957; https://doi.org/10.3390/vaccines13090957 - 8 Sep 2025

Cited by 4 | Viewed by 3080

Abstract

Background/Objectives: Lung cancer remains the leading cause of cancer-related deaths globally, with non-small-cell lung cancer (NSCLC) accounting for most cases. Although advances in targeted therapies and immunotherapy have improved outcomes, long-term survival remains limited. This review aims to explore current immunotherapeutic strategies, [...] Read more.

Background/Objectives: Lung cancer remains the leading cause of cancer-related deaths globally, with non-small-cell lung cancer (NSCLC) accounting for most cases. Although advances in targeted therapies and immunotherapy have improved outcomes, long-term survival remains limited. This review aims to explore current immunotherapeutic strategies, the evolving role of therapeutic cancer vaccines, and the emerging potential of human papillomavirus-targeted interventions in lung cancer, particularly among non-smoker populations. Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and Web of Science databases to identify relevant articles published between 2015 and 2024. Studies focusing on immune checkpoint inhibitors, vaccine platforms, HPV-associated lung cancer, tumor microenvironment modulation, and novel delivery systems such as bacterial ghosts were included. Relevant clinical trials and preclinical studies were critically evaluated and synthesized. Results: Immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4 have demonstrated clinical efficacy in NSCLC, yet their effectiveness is often limited by resistance mechanisms and lack of robust predictive biomarkers. Cancer vaccines, including peptide-based, mRNA, DNA, dendritic cell, and bacterial ghost platforms are emerging as complementary strategies to enhance antitumor immunity. Moreover, accumulating evidence suggests a potential association between high-risk HPV infection and lung cancer development, supporting the rationale for HPV-targeted vaccine strategies. Conclusions: Immunotherapy and therapeutic vaccination hold significant promise in reshaping lung cancer treatment. Advancements in vaccine design, delivery platforms like bacterial ghosts, and better understanding of HPV’s role in lung oncogenesis could support more effective, personalized immunotherapeutic approaches in the future. Full article

(This article belongs to the Special Issue Innovative Vaccines That Modulate the Immune System to Enhance Cancer Therapy)

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19 pages, 283 KB

Open AccessEditor’s ChoiceReview

Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review

by Daniele Zama, Laura Pedretti, Gaia Capoferri, Roberta Forestiero, Marcello Lanari and Susanna Esposito

Vaccines 2025, 13(9), 932; https://doi.org/10.3390/vaccines13090932 - 1 Sep 2025

Cited by 3 | Viewed by 3006

Abstract

Background: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy have markedly improved survival in pediatric patients with hematological malignancies. However, these treatments cause profound immunosuppression, leading to significant susceptibility to vaccine-preventable diseases (VPDs), including invasive pneumococcal disease and measles. Timely [...] Read more.

Background: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy have markedly improved survival in pediatric patients with hematological malignancies. However, these treatments cause profound immunosuppression, leading to significant susceptibility to vaccine-preventable diseases (VPDs), including invasive pneumococcal disease and measles. Timely and tailored immunization strategies are crucial to mitigate infectious risks in this vulnerable population. Methods: We conducted a narrative review of the English-language literature from 2000 to 2024, including clinical guidelines, surveys, and original studies, to evaluate immune reconstitution and vaccination practices in pediatric patients undergoing HCT and CAR-T therapy. Literature searches in PubMed, Scopus, and Web of Science used disease-specific, therapy-specific, and pathogen-specific terms. Data synthesis focused on vaccine schedules, immune recovery markers, and adherence challenges. Results: Profound immune deficits post-HCT and CAR-T therapy compromise both innate and adaptive immunity, often necessitating revaccination. Key factors influencing vaccine responses include time since therapy, graft source, immunosuppressive treatments, and chronic graft-versus-host disease. Although inactivated vaccines are generally safe from three to six months post-HCT, live vaccines remain contraindicated until documented immune recovery. CAR-T therapy introduces unique challenges due to prolonged B-cell aplasia and hypogammaglobulinemia, leading to delayed or reduced vaccine responses. Despite established guidelines, real-world adherence to vaccination schedules remains suboptimal, driven by institutional, logistic, and patient-related barriers. Conclusions: Effective vaccination strategies are essential for reducing infectious morbidity in pediatric HCT and CAR-T recipients. Personalized vaccine schedules, immune monitoring, and multidisciplinary coordination are critical to bridging gaps between guidelines and practice, ultimately improving long-term outcomes for immunocompromised children. Full article

(This article belongs to the Special Issue Childhood Immunization and Public Health)

29 pages, 1172 KB

Open AccessEditor’s ChoiceReview

Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook

by Yiyang Zheng, Yusheng Pei, Chunyan Dong, Jinghui Liang, Tong Cai, Yuan Zhang, Dejiang Tan, Junzhi Wang and Qing He

Vaccines 2025, 13(8), 880; https://doi.org/10.3390/vaccines13080880 - 20 Aug 2025

Cited by 6 | Viewed by 5795

Abstract

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval [...] Read more.

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies. Full article

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25 pages, 376 KB

Open AccessEditor’s ChoiceReview

Research Progress of Universal Influenza Vaccine

by Liangliang Wang, Qian Xie, Pengju Yu, Jie Zhang, Chenchen He, Weijin Huang, Youchun Wang and Chenyan Zhao

Vaccines 2025, 13(8), 863; https://doi.org/10.3390/vaccines13080863 - 15 Aug 2025

Cited by 8 | Viewed by 9234

Abstract

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza [...] Read more.

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza vaccines and their advantages and disadvantages in universal vaccine design. We also summarize the common design strategies for universal influenza vaccines, which mainly include the immunofocusing strategy, multi-target combination strategy, T-cell strategy, computationally optimized broadly cross-reactive antigenic strategy (COBRA), and artificial intelligence strategy. In addition, we also sort out the latest research progress of universal influenza vaccines under different technological routes. This will help researchers better grasp the latest developments of universal influenza vaccines. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

23 pages, 1964 KB

Open AccessEditor’s ChoiceReview

Freeze-Drying of mRNA-LNPs Vaccines: A Review

by MD Faizul Hussain Khan, Floriane Baudin, Ayyappasamy Sudalaiyadum Perumal and Amine A. Kamen

Vaccines 2025, 13(8), 853; https://doi.org/10.3390/vaccines13080853 - 12 Aug 2025

Cited by 18 | Viewed by 7228

Abstract

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA [...] Read more.

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA vaccines by converting them into a stable dry powder. The purpose of this review is to provide an overview of the current knowledge on the progress of freeze-drying techniques for mRNA vaccines, with emphasis on the associated challenges. This review highlights the factors influencing the stability of freeze-dried mRNA vaccines and provides a comprehensive overview of the formulation components, including excipients, buffers, and surfactants, as well as the process parameters and storage conditions that aim to improve stability and shelf-life. By providing these insights, this review supports the advancement of more robust, scalable, and efficient lyophilization protocols, ultimately addressing the stability limitations of mRNA vaccines and enhancing their global accessibility. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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18 pages, 388 KB

Open AccessEditor’s ChoiceReview

A Narrative Review on How Timing Matters: Circadian and Sleep Influences on Influenza Vaccine Induced Immunity

by Achilleas Livieratos, Jamie M. Zeitzer and Sotirios Tsiodras

Vaccines 2025, 13(8), 845; https://doi.org/10.3390/vaccines13080845 - 8 Aug 2025

Cited by 4 | Viewed by 5399

Abstract

We aimed to synthesize and critically evaluate human studies on the impact of circadian and sleep factors on influenza vaccine-induced immune responses. A comprehensive literature review was conducted, and of the 1260 studies identified, 13 met the inclusion criteria for evaluating vaccination timing, [...] Read more.

We aimed to synthesize and critically evaluate human studies on the impact of circadian and sleep factors on influenza vaccine-induced immune responses. A comprehensive literature review was conducted, and of the 1260 studies identified, 13 met the inclusion criteria for evaluating vaccination timing, circadian misalignment, and sleep parameters in relation to influenza vaccine-induced immune responses in human populations. Most studies assessed humoral immune responses, primarily antibody titers. Morning vaccination (typically between 9:00 and 11:00 AM) was associated with higher antibody titers compared to afternoon vaccination, particularly for the A/H1N1 strain in adults aged ≥ 65 years. Short sleep duration—especially in the two nights preceding vaccination—was associated with reduced antibody levels, while acute sleep deprivation the night after vaccination transiently reduced antibody levels in males. Sleep fragmentation and excessive daytime sleepiness were linked to increased vulnerability to breakthrough infections. Evidence on circadian misalignment from shift work was mixed. Clinical outcomes were reported in one large trial, where morning vaccination correlated with fewer respiratory hospitalizations. Current evidence supports a potential role for circadian timing and sleep duration in enhancing vaccine-induced antibody responses, particularly in older adults and individuals with sleep or circadian disruption. However, inconsistencies, modest effect sizes, and methodological limitations preclude broad recommendations. Future studies should incorporate direct measures of circadian phase, stratify by chronotype and population (e.g., shift workers), and evaluate both immunologic and clinical outcomes to inform targeted chrono-immunization strategies. Full article

(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)

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12 pages, 2630 KB

Open AccessEditor’s ChoiceArticle

Evaluating the Relationship Between the Introduction of the Acellular Pertussis Vaccine and Whooping Cough Resurgence in the United States

by Jeegan Parikh, Ismael Hoare and Ricardo Izurieta

Vaccines 2025, 13(8), 841; https://doi.org/10.3390/vaccines13080841 - 7 Aug 2025

Cited by 6 | Viewed by 5663

Abstract

Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United [...] Read more.

Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United States and the change in the type of pertussis vaccines. Methods: Pertussis cases from 1922 to 2024 were obtained from the CDC’s national notifiable disease surveillance system, and vaccination coverage was obtained from the WHO. A trend analysis and Pearson’s correlation test were conducted between the incidence of cases and the coverage of the third and fourth doses of the pertussis vaccine. An ANOVA test and multivariable linear regression were performed to assess the association between the type of vaccine and the number of pertussis cases. Results: The number of cases increased from 4083 in 1992 to 35,435 in 2024, with cyclical outbreaks in 2010, 2012–2014, and 2024. The third and fourth doses of pertussis vaccine coverage had mild and moderate correlations with the number of pertussis cases. The vaccine type had a significant association with the number of pertussis cases and stayed significant after adjusting for vaccination coverage. Conclusions: The switch in pertussis vaccine has impacted the epidemiology of pertussis outbreaks in the United States. A combination of factors, such as different types of immune response to vaccines, waning of immunity, and selection of non-vaccine bacterial strains, may explain the observed results. Further research on newer, improved vaccinations or alternative schedules in children needs to be conducted to address the resurgence of pertussis in this study. Full article

(This article belongs to the Special Issue Vaccination, Public Health and Epidemiology)

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32 pages, 2027 KB

Open AccessEditor’s ChoiceReview

Harnessing the Loop: The Perspective of Circular RNA in Modern Therapeutics

by Yang-Yang Zhao, Fu-Ming Zhu, Yong-Juan Zhang and Huanhuan Y. Wei

Vaccines 2025, 13(8), 821; https://doi.org/10.3390/vaccines13080821 - 31 Jul 2025

Cited by 7 | Viewed by 6977

Abstract

Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and [...] Read more.

Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and modular delivery platforms are accelerating clinical translation. In this review, we synthesize recent advances in circRNA therapeutics, with a focused analysis of their stability and immunogenic properties in vaccine and drug development. Notably, key synthesis strategies, delivery platforms, and AI-driven optimization methods enabling scalable production are discussed. Moreover, we summarize preclinical and emerging clinical studies that underscore the potential of circRNA in vaccine development and protein replacement therapies. As both a promising expression vehicle and programmable regulatory molecule, circRNA represents a versatile platform poised to advance next-generation biologics and precision medicine. Full article

(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)

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23 pages, 1372 KB

Open AccessEditor’s ChoiceArticle

Immunization with Complete Freund’s Adjuvant Reveals Trained Immunity-like Features in A/J Mice

by Kiruthiga Mone, Shraddha Singh, Fatema Abdullatif, Meghna Sur, Mahima T. Rasquinha, Javier Seravalli, Denise K. Zinniel, Indranil Mukhopadhyay, Raul G. Barletta, Teklab Gebregiworgis and Jay Reddy

Vaccines 2025, 13(7), 768; https://doi.org/10.3390/vaccines13070768 - 21 Jul 2025

Cited by 4 | Viewed by 3550

Abstract

Background/Objectives: Freund’s adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund’s adjuvant (CFA) involve the mechanisms of trained immunity (TI). Methods: We examined bone marrow cells (BMCs) [...] Read more.

Background/Objectives: Freund’s adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund’s adjuvant (CFA) involve the mechanisms of trained immunity (TI). Methods: We examined bone marrow cells (BMCs) isolated from CFA-immunized A/J mice to address this question. Incomplete Freund’s adjuvant (IFA) and Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin (BCG) served as negative and positive controls, respectively. We evaluated cytokine profiles, metabolic, and epigenetic changes. Results: First, BMCs from all groups except saline showed varied levels of IL-1β, IL-6, and TNF-α. But expression of CCL5 and CXCL10 was significantly elevated only in the CFA and BCG groups. Transcriptionally, significant elevations were noted for TNF-α and IL-1β in the CFA and BCG groups, whereas CXCL10, IL-6, and IL-10 were upregulated in the CFA and BCG groups, respectively. Second, while BMCs from the BCG group expressed the markers of both the M1 and M2 macrophages, no clear trends were noted in the CFA and IFA groups. Third, cell lysates from the CFA group revealed metabolic reprogramming in the BMCs. Specifically, we observed an increased level of lactate, indicative of aerobic glycolysis, which is implicated in TI, and this was also detected in the IFA group. Fourth, epigenetic analysis revealed histone enrichment in the promoter region of TNF-α, in the CFA group, but to a lesser degree than the BCG group. However, no epigenetic changes were observed in the IFA group. Conclusions: Our data provide new insights into the mechanisms of Freund’s adjuvants and the immunomodulatory effects of CFA could involve the features of TI. Full article

(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)

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67 pages, 4242 KB

Open AccessEditor’s ChoiceReview

Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives

by Ayesha Zahid, Hazrat Ismail, Jennifer C. Wilson and I. Darren Grice

Vaccines 2025, 13(7), 767; https://doi.org/10.3390/vaccines13070767 - 20 Jul 2025

Cited by 20 | Viewed by 9315

Abstract

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic [...] Read more.

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

(This article belongs to the Special Issue Bioengineering Strategies for Developing Vaccines)

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21 pages, 492 KB

Open AccessEditor’s ChoiceReview

Research Progress on Varicella-Zoster Virus Vaccines

by Hongjing Liu, Lingyan Cui, Sibo Zhang, Hong Wang, Wenhui Xue, Hai Li, Yuyun Zhang, Lin Chen, Ying Gu, Tingting Li, Ningshao Xia and Shaowei Li

Vaccines 2025, 13(7), 730; https://doi.org/10.3390/vaccines13070730 - 4 Jul 2025

Cited by 8 | Viewed by 7270

Abstract

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has [...] Read more.

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has substantially reduced the global incidence of these diseases. However, live attenuated vaccines raise concerns regarding safety and immunogenicity, especially in immunocompromised populations, while recombinant subunit vaccines, such as Shingrix, exhibit high efficacy but are associated with side effects and adjuvant limitations. Recent advancements in vaccine technology, including mRNA vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines, offer promising alternatives with improved safety profiles and durable immunity. This review synthesizes current knowledge on VZV vaccine mechanisms, clinical applications, and immunization strategies, while also examining future directions in vaccine development. The findings underscore the pivotal role of VZV vaccines in disease prevention and highlight the need for continued research to enhance their public health impact. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

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12 pages, 631 KB

Open AccessEditor’s ChoiceReview

Challenges and Limitations of Current RSV Prevention Strategies in Infants and Young Children: A Narrative Review

by Nicola Principi, Serafina Perrone and Susanna Esposito

Vaccines 2025, 13(7), 717; https://doi.org/10.3390/vaccines13070717 - 1 Jul 2025

Cited by 12 | Viewed by 5789

Abstract

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal [...] Read more.

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal immunization. While these interventions have improved early protection, several limitations hinder their broader impact and long-term effectiveness. Methods: This narrative review synthesizes evidence from clinical trials, observational studies, and regulatory reports to evaluate the main limitations of nirsevimab and maternal RSV vaccination. Literature searches were conducted in major databases, focusing on efficacy, safety, immunogenicity, implementation, and population-specific challenges. Results: Both nirsevimab and maternal vaccination provide strong protection during the first six months of life, but their effectiveness wanes thereafter. This is concerning as nearly half of RSV-related deaths occur in children over six months old. Maternal vaccine efficacy is uncertain in very-preterm infants, and safety concerns persist, including potential associations with preterm birth, Guillain–Barré syndrome, and hypertensive disorders. Real-world data from low-income countries are lacking, limiting generalizability. Additionally, the risk of vaccine-associated enhanced disease (VAED), although unconfirmed, has delayed pediatric vaccine development. Emerging monoclonal antibodies and live-attenuated vaccines are under investigation to extend protection beyond infancy. Conclusions: Despite substantial progress, current RSV prevention strategies leave critical gaps, particularly for older infants and underserved populations. There is a pressing need for next-generation vaccines, enhanced pharmacovigilance, and equitable global implementation to ensure sustained and inclusive RSV protection. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)

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21 pages, 323 KB

Open AccessEditor’s ChoiceReview

Progress and Recent Developments in HIV Vaccine Research

by Iris Shim, Lily Rogowski and Vishwanath Venketaraman

Vaccines 2025, 13(7), 690; https://doi.org/10.3390/vaccines13070690 - 26 Jun 2025

Cited by 12 | Viewed by 16133

Abstract

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of [...] Read more.

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article

(This article belongs to the Special Issue Advances in HIV Vaccine Development, 2nd Edition)

15 pages, 2783 KB

Open AccessEditor’s ChoiceArticle

Childhood Immunization Coverage Before, During and After the COVID-19 Pandemic in Italy

by Flavia Pennisi, Andrea Silenzi, Alessia Mammone, Andrea Siddu, Anna Odone, Michela Sabbatucci, Riccardo Orioli, Anna Carole D’Amelio, Francesco Maraglino, Giovanni Rezza and Carlo Signorelli

Vaccines 2025, 13(7), 683; https://doi.org/10.3390/vaccines13070683 - 25 Jun 2025

Cited by 6 | Viewed by 3726

Abstract

Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate [...] Read more.

Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate national and regional trends in vaccine coverage across three phases: post-mandate (2015–2016 vs. 2017–2019), pandemic (2017–2019 vs. 2020–2021), and post-pandemic recovery (2020–2021 vs. 2022–2023). Methods: National and regional administrative data on vaccination coverage at 24 months of age were obtained from the Italian Ministry of Health. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs), and absolute changes in coverage (Δ) were calculated across defined periods. Pearson correlation coefficients were used to assess associations between baseline coverage and subsequent changes. Results: After the 2017 mandate, coverage increased significantly for varicella (APC = +28.6%), MenB (+22.6%), and measles (+3.4%). Regionally, varicella coverage rose by up to +58.4% in Emilia-Romagna and measles by +11.1% in Campania. During the pandemic, coverage declined for polio (−2.4% in the South) and measles (−6.2% in Abruzzo), while MenB increased in regions with lower initial uptake (r = −0.918, p < 0.001). Post-pandemic, coverage rebounded, with varicella improving by +20.1% in central regions and measles by +13.9% in Abruzzo. A strong inverse correlation between baseline coverage and improvement was observed for varicella across all periods (r from −0.877 to −0.915). Conclusions: Mandatory vaccination policies led to substantial coverage improvements, and despite the disruption caused by the pandemic, recovery trends were observed for most vaccines. The consistent association between low baseline coverage and stronger gains highlights the resilience of the system, but also the ongoing need for regionally tailored strategies to reduce geographic disparities and ensure equitable immunization across Italy. Full article

(This article belongs to the Section Vaccines and Public Health)

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15 pages, 421 KB

Open AccessEditor’s ChoiceReview

VITT Pathophysiology: An Update

by Eleonora Petito and Paolo Gresele

Vaccines 2025, 13(6), 650; https://doi.org/10.3390/vaccines13060650 - 17 Jun 2025

Cited by 3 | Viewed by 3237

Abstract

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation [...] Read more.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation in the presence of PF4. In addition to this immune-based pathomechanism, random splicing events of the Adv-vector DNA encoding for SARS-CoV-2 spike protein resulting in the secretion of soluble spike variants have been postulated as a possible pathophysiological mechanism. More recently, some novel clinical-pathological anti-PF4-associated entities also characterized by thrombosis, thrombocytopenia, and VITT-like antibodies but independent from heparin or AdV-vaccine administration have been identified. To date, these VITT-like disorders have been reported following the administration of vaccines different from anti-SARS-CoV-2 AdV-vaccines, like human papillomavirus (HPV) and mRNA-based COVID-19 vaccines, following a bacterial or viral respiratory infection, and in patients with a monoclonal gammopathy of undetermined significance. The purpose of this review is to provide an update on the knowledge on VITT pathogenesis, focusing on recent findings on anti-PF4 antibodies, on a possible genetic predisposition to VITT, on VITT-antibody intracellular activated pathways, on lipid metabolism alterations, and on new VITT-like disorders. Full article

(This article belongs to the Special Issue Vaccine-Induced Immune Thrombotic Thrombocytopenia)

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17 pages, 312 KB

Open AccessEditor’s ChoiceReview

Human Alpha Herpesviruses Infections (HSV1, HSV2, and VZV), Alzheimer’s Disease, and the Potential Benefits of Targeted Treatment or Vaccination—A Virological Perspective

by Peter A. C. Maple and Akram A. Hosseini

Vaccines 2025, 13(6), 572; https://doi.org/10.3390/vaccines13060572 - 27 May 2025

Cited by 5 | Viewed by 7097

Abstract

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) [...] Read more.

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

16 pages, 7103 KB

Open AccessEditor’s ChoiceArticle

Adjuvanted RNA Origami—A Tunable Peptide Assembly Platform for Constructing Cancer Nanovaccines

by Theresa Yip, Xinyi Tu, Xiaodong Qi, Hao Yan and Yung Chang

Vaccines 2025, 13(6), 560; https://doi.org/10.3390/vaccines13060560 - 25 May 2025

Cited by 5 | Viewed by 2711

Abstract

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as [...] Read more.

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG. Methods: Here, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity. Results: Although the vaccines with a high number of peptides, i.e., 100–200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8⁺ T cell responses against engrafted tumor cells, probably owing to an induction of early T cell exhaustion. Interestingly, the same vaccine format with a low number of peptides, i.e., 10–15 peptides/RNA-OG, enhanced CD8⁺ T cell responses without provoking T cell exhaustion in tumor-bearing mice, leading to strong protective anti-tumor immunity. In comparison, the covalently assembled RNA-OG-peptide vaccine, having a similarly low peptide dosage, offered the highest therapeutic efficacy. Thus, our RNA-OG nanostructure provides a simple and tunable platform for peptide loading to optimize vaccine efficacy. Conclusions: Our findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy. Full article

(This article belongs to the Special Issue Novel Immunotherapies, Cell Therapies and Cancer Vaccines)

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22 pages, 5356 KB

Open AccessEditor’s ChoiceArticle

Mucosal and Serum Neutralization Immune Responses Elicited by COVID-19 mRNA Vaccination in Vaccinated and Breakthrough-Infection Individuals: A Longitudinal Study from Louisville Cohort

by Lalit Batra, Divyasha Saxena, Triparna Poddar, Maryam Zahin, Alok Amraotkar, Megan M. Bezold, Kathleen T. Kitterman, Kailyn A. Deitz, Amanda B. Lasnik, Rachel J. Keith, Aruni Bhatnagar, Maiying Kong, Jon D. Gabbard, William E. Severson and Kenneth E. Palmer

Vaccines 2025, 13(6), 559; https://doi.org/10.3390/vaccines13060559 - 24 May 2025

Cited by 4 | Viewed by 2361

Abstract

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the [...] Read more.

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development: 2nd Edition)

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20 pages, 986 KB

Open AccessEditor’s ChoiceReview

Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review

by Justin Tang, Md Al Amin and Jian L. Campian

Vaccines 2025, 13(5), 524; https://doi.org/10.3390/vaccines13050524 - 15 May 2025

Cited by 25 | Viewed by 12000

Abstract

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often [...] Read more.

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article

(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)

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24 pages, 592 KB

Open AccessEditor’s ChoiceReview

Addressing the Underestimated Burden of RSV in Older Adults in Europe: Epidemiology, Surveillance Gaps, and Public Health Implications

by Floriana D’Ambrosio, Marta Lomazzi, Michael Moore, Ada Maida, Roberto Ricciardi, Ludovica Munno, Monia Lettieri, Elisabetta De Vito, Walter Ricciardi and Giovanna Elisa Calabrò

Vaccines 2025, 13(5), 510; https://doi.org/10.3390/vaccines13050510 - 12 May 2025

Cited by 13 | Viewed by 7043

Abstract

Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating [...] Read more.

Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating the burden in older and high-risk adults. This review aims to synthesize current evidence on the epidemiological and clinical impact of RSV in older adults in Europe, assess existing surveillance strategies, and identify gaps to guide targeted public health responses. Methods: A two-phase research strategy was adopted. First, a comprehensive review of studies published between 2015–2025 was conducted via PubMed, focusing on the RSV burden in high-risk and elderly populations in Europe. Second, a structured web screening was performed to assess the status of existing RSV surveillance systems, focusing on eight selected European countries. Results: The review reported RSV prevalence rates ranging from 1% to 64.7% among older adults, with a high prevalence of comorbidities that exacerbate disease severity. Hospitalization rates varied between 12.6–55.9%, while mortality ranged from 2.15% to 13%, reaching up to 36% in intensive care settings. Surveillance systems for adult RSV infections across Europe remain limited and fragmented, with only 37.5% (3/8) of analyzed countries having dedicated surveillance for adults. Conclusions: RSV represents a substantial and underrecognized threat to older adults, with significant clinical and healthcare implications. Strengthening surveillance, standardizing data collection, and ensuring equitable access to newly available preventive measures are urgent priorities to reduce the disease burden, protect vulnerable populations, and support resilient health systems against future health challenges. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)

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13 pages, 231 KB

Open AccessEditor’s ChoiceReview

Dengue Vaccine Development and Deployment into Routine Immunization

by Annelies Wilder-Smith, Thomas Cherian and Joachim Hombach

Vaccines 2025, 13(5), 483; https://doi.org/10.3390/vaccines13050483 - 29 Apr 2025

Cited by 15 | Viewed by 8453

Abstract

Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly [...] Read more.

Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly in high-burden regions. TAK-003, a tetravalent live-attenuated vaccine, has demonstrated 61% efficacy against virologically confirmed dengue and 84% efficacy against hospitalizations in endemic settings. However, concerns remain about vaccine-enhanced disease, particularly among seronegative individuals exposed to DENV3 and DENV4. WHO recommends targeted introduction in high-transmission settings without pre-vaccination screening, while ongoing post-introduction studies will further clarify long-term safety and efficacy. Effective vaccine rollout requires a multi-pronged approach, including school-based immunization, integration with adolescent health services, and strong community engagement. Decision-making for vaccine introduction should be guided by National Immunization Technical Advisory Groups (NITAGs), local epidemiological data, and cost-effectiveness assessments. While future vaccines, including mRNA and virus-like particle candidates, are under development, optimizing the use of currently available vaccines is crucial to reducing dengue’s public health impact. Given the continued rise in cases, immediate action—combining vaccination with vector control—is essential to prevent further morbidity and mortality. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

19 pages, 3320 KB

Open AccessEditor’s ChoiceArticle

Generation of Chimeric African Swine Fever Viruses Through In Vitro and In Vivo Intergenotypic Gene Complementation

by Tomoya Kitamura, Kentaro Masujin, Mitsutaka Ikezawa, Aruna Ambagala and Takehiro Kokuho

Vaccines 2025, 13(5), 462; https://doi.org/10.3390/vaccines13050462 - 25 Apr 2025

Cited by 10 | Viewed by 2888

Abstract

Background/Objectives: African swine fever (ASF), a fatal febrile hemorrhagic disease in domestic pigs and Eurasian wild boars, is caused by ASF virus (ASFV). ASF continues to spread across the globe, causing a significant impact on the world’s pig industry. Recently, highly virulent [...] Read more.

Background/Objectives: African swine fever (ASF), a fatal febrile hemorrhagic disease in domestic pigs and Eurasian wild boars, is caused by ASF virus (ASFV). ASF continues to spread across the globe, causing a significant impact on the world’s pig industry. Recently, highly virulent chimeric ASFV (chASFV) strains with recombined genomes of the p72 genotype I and II viruses have been reported in China, Vietnam and Russia. Methods: In order to understand the propensity of ASFV genome for recombination, we attempted to experimentally generate chASFVs both in vitro and in vivo employing two distinct attenuated ASFV strains: OUR T88/3 (genotype I) and AQSΔB119L (genotype II). Results: When IPKM cells were co-infected with ASFV OUR T88/3 and AQSΔB119L strains, three genetically distinct chASFV emerged. When pigs were inoculated with the individual chASFV isolates, all pigs developed acute ASF. When four pigs were co-infected with ASFV OUR T88/3 and AQSΔB119L, all of them developed acute ASF and died or were euthanized. Three chASFV strains were successfully isolated from splenic homogenates from each pig. Conclusions: Our research indicates that genotype I and II chASFV with diverse genomes can be easily generated experimentally both in vitro and in vivo. Full article

(This article belongs to the Section Veterinary Vaccines)

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19 pages, 689 KB

Open AccessEditor’s ChoiceReview

Maternal Immunization: Current Evidence, Progress, and Challenges

by Veronica Santilli, Mayla Sgrulletti, Giorgio Costagliola, Alessandra Beni, Maria Felicia Mastrototaro, Davide Montin, Caterina Rizzo, Baldassarre Martire, Michele Miraglia del Giudice and Viviana Moschese

Vaccines 2025, 13(5), 450; https://doi.org/10.3390/vaccines13050450 - 24 Apr 2025

Cited by 13 | Viewed by 11213

Abstract

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations [...] Read more.

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases. Full article

(This article belongs to the Special Issue Vaccines for the Vulnerable Population)

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22 pages, 723 KB

Open AccessEditor’s ChoiceReview

From Antibodies to Immunity: Assessing Correlates of Flavivirus Protection and Cross-Reactivity

by Hannah E. Flores, Eduar Fernando Pinzon Burgos, Sigrid Camacho Ortega, Alonso Heredia and Joel V. Chua

Vaccines 2025, 13(5), 449; https://doi.org/10.3390/vaccines13050449 - 24 Apr 2025

Cited by 7 | Viewed by 4712

Abstract

Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), [...] Read more.

Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), which help indicate host immunity after vaccination. Current vaccines primarily focus on neutralizing antibodies (nAbs) against the viral envelope E protein, though emerging evidence suggests other potential targets may also be effective in disease prevention. Additionally, there is growing evidence of cross-protection between different flaviviruses when immunity to one virus is achieved, although this can be limited by antibody-dependent enhancement. This review examines the current understanding of flavivirus immunity, CoPs, and the potential for cross-protection in the context of existing vaccine strategies. Full article

(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)

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27 pages, 819 KB

Open AccessEditor’s ChoiceReview

HPV Vaccine Delivery Strategies to Reach Out-of-School Girls in Low- and Middle-Income Countries: A Narrative Review

by Erica N. Rosser, Megan D. Wysong, Joseph G. Rosen, Rupali J. Limaye and Soim Park

Vaccines 2025, 13(5), 433; https://doi.org/10.3390/vaccines13050433 - 22 Apr 2025

Cited by 9 | Viewed by 5708

Abstract

Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented [...] Read more.

Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented through school-based immunization platforms. Unfortunately, this strategy risks missing out-of-school (OOS) girls (i.e., girls not enrolled in formal schools). This narrative review maps the literature and synthesizes existing evidence on service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Methods: Using relevant databases, we conducted a narrative review of published, peer-reviewed literature to map and synthesize the existing evidence on effective service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Results: The 21 articles identified presented findings on strategies to reach OOS girls, with the most frequently cited strategies being facility-based and community outreach approaches. Authors also described community-based strategies used to identify and enumerate OOS girls, including peer tracing, church outreach initiatives, as well as partnerships with local groups (e.g., civil service organizations) and individuals (e.g., healthcare workers, teachers). The articles discussed barriers at the individual (e.g., lack of parental consent), facility/program delivery (e.g., lack of transportation for vaccines), and community (e.g., distance from homes to vaccination services) levels to HPV vaccine delivery, as well as solutions at the facility/program delivery (e.g., pilot programs) and community (e.g., multi-level partnerships) levels. Conclusions: Additional research is needed to evaluate implementation strategies targeting OOS girls with HPV vaccination. A better understanding of these strategies can provide valuable insights for HPV vaccine policymakers, healthcare providers, and program implementers. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)

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12 pages, 1557 KB

Open AccessEditor’s ChoiceArticle

Neutralizing Antibody Response to the AreXvy Respiratory Syncytial Virus Vaccine in Lung Transplant Recipients: Assessment Against Reference and Seasonal Strains

by Liran Levy, Dafna Yahav, Mark Benzimra, Yael Bezalel, Tomer Hoffman, Neta Shirin, Tomer Sinai, Menucha Jurkowicz, Ofir Deri, Noa Matalon, Milton Saute, Yaniv Lustig, Eyal Nachum, Michael Peled, Ital Nemet and Michal Mandelboim

Vaccines 2025, 13(4), 398; https://doi.org/10.3390/vaccines13040398 - 11 Apr 2025

Cited by 5 | Viewed by 2851

Abstract

Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy^® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity [...] Read more.

Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy^® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity in solid organ transplant recipients remain unclear. Methods: A single-center retrospective cohort study, including all LTx recipients who were vaccinated with Arexvy in February 2024. Baseline and follow-up serum samples (1, 3, and 6 months post-vaccination) were analyzed for antibody responses using a commercial RSV ELISA kit and micro-neutralization assays against historical reference RSV A/B ATCC strains and seasonal RSV strains. Adverse events were documented. Results: A total of 28 recipients received the vaccine. Twenty-one (75%) were male, and the median age was 62 years (interquartile range [IQR], 53–67). The median time from transplant was 486 days (IQR, 243–966). Vaccination elicited strong immunogenic responses, demonstrating a twofold increase in ELISA-determined antibody levels at one month post-vaccination, which were sustained for six months. At one month, 67% of recipients had antibody levels exceeding the cutoff threshold. Micro-neutralization assays showed a significant increase in neutralizing antibodies against all tested variants (RSV A/B ATCC and seasonal RSV A/B), with titers remaining at least twofold higher than pre-vaccination levels. No serious adverse events were observed. Conclusions: Our findings demonstrate a sustained antibody response to the Arexvy^® vaccine in a cohort of LTx recipients, with antibody titers sustained over six months. Further research is needed to assess the long-term durability of the immune response and the potential immunogenicity of this vaccine in LTx populations. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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17 pages, 267 KB

Open AccessEditor’s ChoiceReview

The Application of mRNA Technology for Vaccine Production—Current State of Knowledge

by Anna Paczkowska, Karolina Hoffmann, Agata Andrzejczak, Weronika Faustyna Pucek, Dorota Kopciuch, Wiesław Bryl, Elżbieta Nowakowska and Krzysztof Kus

Vaccines 2025, 13(4), 389; https://doi.org/10.3390/vaccines13040389 - 4 Apr 2025

Cited by 5 | Viewed by 6869

Abstract

Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability [...] Read more.

Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability to trigger an immune response), and solving the challenge of delivering mRNA into cells—all to achieve a therapeutic effect. The aim of this study was to review the scientific literature on the use of mRNA technology in the production of vaccines. Various methods of applying mRNA technology that could potentially be introduced into clinical practice in the future are described. A detailed analysis was conducted on the approved COVID-19 vaccines developed by Pfizer/BioNTech (New York, NY, USA) and Moderna (Kirkland, QC, Canada), as their introduction marked a groundbreaking moment in the advancement of mRNA technology. This study was based on the latest scientific literature from reputable publishers and medical databases such as PubMed and ClinicalTrials. In conclusion, mRNA technology is currently experiencing rapid development, significantly driven by the ongoing COVID-19 pandemic. The application of this technology holds great potential not only for vaccines against infectious diseases but also for cancer treatment. However, further research is necessary to facilitate its broader clinical implementation. Full article

(This article belongs to the Special Issue Vaccine Development and Global Health)

25 pages, 1446 KB

Open AccessEditor’s ChoiceReview

Exploring CD169⁺ Macrophages as Key Targets for Vaccination and Therapeutic Interventions

by Rianne G. Bouma, Aru Z. Wang and Joke M. M. den Haan

Vaccines 2025, 13(3), 330; https://doi.org/10.3390/vaccines13030330 - 20 Mar 2025

Cited by 9 | Viewed by 6332

Abstract

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages [...] Read more.

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169⁺ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169⁺ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169⁺ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169⁺ macrophages in several disease settings and the vaccination strategies currently under investigation. Full article

(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)

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27 pages, 2149 KB

Open AccessEditor’s ChoiceArticle

Inflammatory and Humoral Immune Responses to Commercial Autogenous Salmonella Bacterin Vaccines in Light-Brown Leghorn Pullets: Primary and Secondary Vaccine Responses

by Chrysta N. Beck, Jossie M. Santamaria and Gisela F. Erf

Vaccines 2025, 13(3), 311; https://doi.org/10.3390/vaccines13030311 - 13 Mar 2025

Cited by 6 | Viewed by 2156

Abstract

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial [...] Read more.

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4⁺ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article

(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)

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19 pages, 2598 KB

Open AccessEditor’s ChoiceArticle

Prime-Boost Vaccination Based on Nanospheres and MVA Encoding the Nucleoprotein of Crimean-Congo Hemorrhagic Fever Virus Elicits Broad Immune Responses

by Eva Calvo-Pinilla, Sandra Moreno, Natalia Barreiro-Piñeiro, Juana M. Sánchez-Puig, Rafael Blasco, José Martínez-Costas, Alejandro Brun and Gema Lorenzo

Vaccines 2025, 13(3), 291; https://doi.org/10.3390/vaccines13030291 - 10 Mar 2025

Cited by 2 | Viewed by 2665

Abstract

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized [...] Read more.

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized nowadays for this particular virus. As CCHF (Crimean–Congo hemorrhagic fever) is a serious threat to public health, there is an urgent need to investigate the development of safe and effective vaccination strategies further. Methods: In this work, we have employed two immunization platforms based on protein nanoparticles and a modified vaccinia Ankara (MVA) viral vector using the nucleoprotein (NP) as the target antigen. The humoral and cellular immune responses were characterized by ELISA, ICS, and cytokine measurement. Results: This work shows that a single dose of the vaccine candidates was not as immunogenic as the heterologous vaccination using nanoparticles and MVA. A prime with NP nanoparticles (NS-NP) and a boost with MVA-expressing NP were capable of triggering significant levels of humoral and cellular immune responses against CCHFV in mice. Conclusions: Our study shows that the NS-NP/MVA-NP vaccination strategy effectively elicits a robust humoral and cellular immune response in a mouse model, emphasizing its potential as a protective approach against CCHFV lineages. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

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14 pages, 1648 KB

Open AccessEditor’s ChoiceArticle

Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4

by Bettina Wagner, Christiane L. Schnabel and Alicia Rollins

Vaccines 2025, 13(3), 290; https://doi.org/10.3390/vaccines13030290 - 10 Mar 2025

Cited by 5 | Viewed by 1745

Abstract

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and [...] Read more.

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

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19 pages, 2176 KB

Open AccessEditor’s ChoiceArticle

Evaluating the Immunogenicity of an Intranasal Microparticle Combination Vaccine for COVID-19 and Influenza

by Sharon Vijayanand, Smital Patil, Priyal Bagwe, Revanth Singh, Emmanuel Adediran and Martin J. D’Souza

Vaccines 2025, 13(3), 282; https://doi.org/10.3390/vaccines13030282 - 7 Mar 2025

Cited by 2 | Viewed by 3040

Abstract

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination [...] Read more.

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination rates. To address the burden of frequent painful injections, this manuscript explores the potential of non-invasive intranasal (IN) vaccine administration as an effective alternative to intramuscular (IM) shots. Further, as a proof-of-concept, an inactivated combination vaccine for COVID-19 and influenza was tested to eliminate the need for separate vaccinations. Methods: The methods involved encapsulating antigens and adjuvants in poly(lactic-co-glycolic acid) (PLGA) polymer matrices, achieving over 85% entrapment. The vaccine was evaluated in vitro for cytotoxicity and immunogenicity before being administered to 6–8-week-old Swiss Webster mice at weeks 0, 3, and 6. The mice were then assessed for antibody levels and cellular responses. Results: The intranasal microparticle (IN-MP) vaccine induced an innate immune response, autophagy, and were non-cytotoxic in vitro. In vivo, the vaccine led to high levels of virus-specific serum IgM, IgG, and IgA binding antibodies, as well as elevated IgG and IgA levels in the lung wash samples. The antibodies generated demonstrated neutralizing activity against the SARS-CoV-2 pseudovirus. Furthermore, the IN-MP vaccine prompted increased antigen-specific CD4⁺ and CD8⁺ T-cell responses in the vaccinated mice. Conclusions: The IN-MP combination vaccine produced immune responses comparable to or higher than the IM route, indicating its potential as an alternative to IM injections. Full article

(This article belongs to the Special Issue Innovating Vaccine Research in Mucosal Vaccines)

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